Myocardial ischemia and severe arrhythmias have been described in acute systemic allergic reactions in humans. Cardiac hypersensitivity reactions will be elicited in the experimental animal, as a first step in the assessment of cardiac hypersensitivity as a clinical problem. Thus, we will pursue the cardiovascular pharmacology of the various mediators of immediate hypersensitivity, i.e. histamine, prostaglandins, slow reacting substance of anaphylaxis (SRS-A) and platelet activating factor (PAF), in the hearts of guinea pigs, rabbits and monkeys, which will have been sensitized to various allergens. Models of IgE-mediated cardiac hypersensitivity reactions will also be investigated. Concentration-response relationships will be sought between released mediators and extent of cardiac dysfunction. Interactions between released mediators and various disease states and drugs, i.e. myocardial ischemia, hypertension, hyperthyroidism, digitalis, diuretics, will be investigated. Pharmacologic means will be sought for correcting and controlling the cardiac dysfunctions caused by immediate hypersensitivity reactions. It will also be ascertained whether autacoid release, particularly histamine, may be implicated in various cardiac pathophysiological events, such as ischemic arrhythmias, digitalis toxicity and hyperthyroidism. Since histamine can be released at any site by any means, this work will permit an appreciation of the cardiac response to autacoids and might uncover mechanistic aspects of common disease states that have been completely overlooked.